The effects of midazolam and ephedrine on post-exercise autonomic chronotropic control of the heart in normal subjects

Abstract

Benzodiazepines may induce hypotension by inhibiting the pressor response. Ephedrine has adrenergic effects on the circulation. After exercise, changes in cardiovascular control impair orthostatic tolerance. The impaired pressure response can be compensated for by chronotropic control of the heart. We studied the effect of midazolam and ephedrine on post-exercise cardiac autonomic chronotropic control in six 21-year-old female volunteers, who received single doses of 15 mg midazolam, 50 mg ephedrine, or placebo orally according to a placebo-controlled, double-blind, crossover design. After exercise, the subjects assumed the supine position for rest, then a -10 degrees head-down position followed by a 70 degrees head-up position. Power spectral analysis of heart rate variability for 7 min and steady-state brachial arterial blood pressure were measured in each position. After administration of midazolam, three subjects had an abnormal fall in their arterial blood pressure (with one presyncope) as a response to head-up tilt. Changes in heart rate variability exceeded those seen during placebo treatment (p < 0.01) and involved oscillations, suggesting activation of both sympathetic and parasympathetic dynamics. After ephedrine administration, arterial blood pressure increased during head-down tilt, but parasympathetic dynamics to the heart were dampened. Head-up tilt induced increased sympathetic stimulation of the heart and a sympathicotonic cardiovascular response (p < 0.01). In conclusion, midazolam induced unexpectedly great changes in dynamic cardiac control during cardiovascular stimulation. Ephedrine increased tonic sympathetic activity and stabilized the neural circulatory control of the heart by immobilizing dynamic parasympathetic activation.

A central γ-aminobutyric acid mechanism in cardiac vagal control in man revealed by studies with intravenous midazolam

“…However, Boralessa et al [29] found that 0.3 mg\kg intravenous midazolam (some four times the present dose) caused a major reduction in the rise in blood pressure normally associated with intubation in man, which is not the same as a decrease in blood pressure in a resting semi-supine patient. Similarly, Lindqvist et al [9] observed that the blood pressure change, notably a fall in arterial blood pressure as a response to head-up tilt, was greater than normal after the administration of a single oral dose of 15 mg of midazolam, again a much higher dose than we have used. In the present study it was observed that administration of midazolam at either of the quite low-dose levels failed to elicit any significant changes in blood pressure at semi-supine rest.…”

“…The effect of benzodiazepines on heart rate and blood pressure in man has been investigated by several groups [5][6][7][8][9], but these studies were not designed to determine the role of GABA synapses in cardiac vagal pathways. Marty et al [5] examined the anaesthetic effects of diazepam and midazolam on baroreflex control of heart rate, showing that large doses of these drugs depress the sensitivity of the reflex.…”

Antipsychotic Pharmacotherapy and Orthostatic Hypotension

“…clonidine, guanfacine) [68] Benzodiazepines (e.g. midazolam, alprazolam, lorazepam), especially when given parenterally [69,70] Dopamine agonists (e.g. pramipexole, ropinirole) and levodopa [71,72] Intravascular volume contraction Diuretics (e.g.…”

Effect of Conscious Sedation on Cardiac Autonomic Regulation during Colonoscopy

“…While the clinical effect of midazolam given intravenously for premedication lasts at least 32 min (35), the disappearance of the drug effect seems unlikely. As stated above, it has been suggested that midazolam potentiates changes in HRV during gravitational stimulation of the cardiovascular system (23). Therefore, it seems logical that midazolam may also potentiate changes in HRV induced by looping of the colonoscope and distention of the bowel.…”

“…However, midazolam has well-documented effects on the cardiovascular system, of which some are potentially dangerous (19). Moreover, there is evidence that midazolam can influence cardiovascular autonomic regulation (20)(21)(22)(23)(24)(25).…”